The evidence is unequivocal that cancer can be induced in people by radiation or by chemicals (including those used in the treatment of cancer). However, little is known about the combined effects of these two agents. People at large can be expected to be exposed to doses protracted more or less over their lifetimes. Although the doses can be expected to be small, such protractions in general will involve contemporaneous exposures to two or more agents. Therefore, in addition to the uncertainties in predicting hazards to public health from a single agent when low doses at effectively low dose rates are involved, the risks due to combinations of agents are even more uncertain because of the potential for interactive effects. The purpose of this research is to initiate a systematic study of the combined effects of protracted exposure (i.e., multifractionation or low-dose-rate rate exposure) on the induction of neoplastic transformation of mammalian cells in culture. Initially the C3H mouse line, designated 10T-1/2, will be used since a significant amount of data for radiation exposure, or for chemical exposure, already exist. As the work progresses, other animal cells, as well as human cells, will be used to establish generalizations. The initial departure of the research will be to determine whether or not members of different classes of chemicals (e.g., directly and indirectly acting mutagens and carcinogens, promoters, antipromoters, etc.) and radiation (ionizing and nonionizing radiation) act independently, or interactively. To such measurements will be added mechanistic studies to determine the nature of any interactive effects, the contribution of repair (or misrepair) processes, and the possible role of cell-surface receptors in modulating responses. These studies are also relevant to cancer treatment. As therapy becomes more effective and lifespans are extended, the risks of inducing second tumors will have to be faced. The induction of second tumors is already well documented in some instances. This work may lead to strategies to minimize such risks.